Objective
Diabetes affects some 500 million people worldwide (estimated 700 million by 2045), causing over one million deaths annually. The disease results from the loss / dysfunction of pancreatic islet insulin-producing β-cells, leading to chronic hyperglycemia and severe complications. Current treatments are symptomatic and fail to restore long-term glucose regulation, stressing the need for a transformative curative approach.
Our proposal leverages α-cell reprogramming as a novel therapy for the restoration of insulin-production in situ, i.e. in the pancreas of diabetics. Islet α-cells remain abundant in diabetic patients and, along with δ- and γ-cells, they possess intrinsic plasticity, meaning that they can “learn” to produce insulin (Nature, 2010 & 2014; Diab Obes Metab, 2016; Nat Cell Biol, 2018; Nat Comm, 2021). Recently, we have shown that if all islet non-β-cells were converted into insulin producers, the islets containing only insulin-producing cells would be perfectly viable and functional, keeping optimal glucose homeostasis (Nat Metab, 2024). We have also reported that genetically reprogrammed human α-cells can secrete insulin and restore normal glucose levels when transplanted to diabetic mice (Nature, 2019). These findings establish islet non-β-cell reprogramming as a viable innovative strategy for diabetes cure.
Here, we aim at developing a first-in-class, non-genetic therapy to induce in situ α-cell reprogramming using small molecules. From a targeted screening we identified six FDA-approved compounds that induce insulin expression above a reprogramming threshold in purified α-cells from 2 donors. We will now explore their mechanism of action re the functional conversion and conduct preclinical studies in healthy and diabetic mice to assess reprogramming efficiency in both endogenous and transplanted human cells. If successful, this approach could transform diabetes therapy, offering a safe and clinically viable alternative to current treatments.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-POC
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1211 Geneve
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.